[ARDS Diagnostics and Treatment after the Coronavirus Pandemic - Everything as it was?] / ARDS-Diagnostik und -Therapie nach der Coronapandemie ­ alles beim Alten?

ARDS is a syndrome that can develop as a result of various underlying diseases. For a long time, the prevailing belief was that the course of the disease was comparable regardless of the underlying disease. However, even before the COVID-19 pandemic, it was suspected that there were different manifestations that could be treated more individually and thus reduce the high mortality rate of ARDS, which has remained unchanged for years. The various findings on the heterogeneity of the course of the disease in COVID-related ARDS appear to confirm these assumptions. It is therefore to be expected that the diagnosis and treatment of non-COVID-related ARDS will also have to be individualised according to such phenotypes in the future. However, as long as the effectiveness of such strategies has not been proven in clinical trials, the current recommendations for ARDS therapy will remain valid for the time being. However, the adjustments already formulated in this context to individual pathophysiological conditions with regard to respiratory mechanics, ventilation-perfusion distribution and possible cardiac dysfunction should be made more meticulously than has usually been the case to date.

Validation of RESP and PRESERVE score for ARDS patients with pumpless extracorporeal lung assist (pECLA).

BACKGROUND: RESP score and PRESERVE score have been validated for veno-venous Extracorporeal Membrane Oxygenation in severe ARDS to assume individual mortality risk. ARDS patients with low-flow Extracorporeal Carbon Dioxide Removal, especially pumpless Extracorporeal Lung Assist, have also a high mortality rate, but there are no validated specific or general outcome scores. This retrospective study tested whether these established specific risk scores can be validated for pumpless Extracorporeal Lung Assist in ARDS patients in comparison to a general organ dysfunction score, the SOFA score. METHODS: In a retrospective single center cohort study we calculated and evaluated RESP, PRESERVE, and SOFA score for 73 ARDS patients with pumpless Extracorporeal Lung Assist treated between 2002 and 2016 using the XENIOS iLA Membrane Ventilator. Six patients had a mild, 40 a moderate and 27 a severe ARDS according to the Berlin criteria. Demographic data and hospital mortality as well as ventilator settings, hemodynamic parameters, and blood gas measurement before and during extracorporeal therapy were recorded. RESULTS: Pumpless Extracorporeal Lung Assist of mechanical ventilated ARDS patients resulted in an optimized lung protective ventilation, significant reduction of PaCO2, and compensation of acidosis. Scoring showed a mean score of alive versus deceased patients of 3 ± 1 versus - 1 ± 1 for RESP (p < 0.01), 3 ± 0 versus 6 ± 0 for PRESERVE (p < 0.05) and 8 ± 1 versus 10 ± 1 for SOFA (p < 0.05). Using receiver operating characteristic curves, area under the curve (AUC) was 0.78 (95% confidence interval (CI) 0.67-0.89, p < 0.01) for RESP score, 0.80 (95% CI 0.70-0.90, p < 0.0001) for PRESERVE score and 0.66 (95% CI 0.53-0.79, p < 0.05) for SOFA score. CONCLUSIONS: RESP and PRESERVE scores were superior to SOFA, as non-specific critical care score. Although scores were developed for veno-venous ECMO, we could validate RESP and PRESERVE score for pumpless Extracorporeal Lung Assist. In conclusion, RESP and PRESERVE score are suitable to estimate mortality risk of ARDS patients with an arterio-venous pumpless Extracorporeal Carbon Dioxide Removal.

[ARDS - An Update - Part 2: Therapy and Outcome]. / ARDS ­ Ein Update ­ Teil 2: Therapie und Outcome.

The Acute Respiratory Distress Syndrome (ARDS) is defined by hypoxemic respiratory failure due to inflammatory response within the lung usually requiring invasive mechanical ventilation. Despite more than 50 years of scientific research numerous issues especially regarding mechanical ventilation as the most important treatment option remain unclear. Most important, adjustment of mechanical ventilation is challenging due to desirable beneficial effects on pulmonary gas exchange on the one hand and deleterious effects in terms of ventilator-associated lung injury on the other. Specifically, optimal settings of positive end-expiratory pressure and the role of spontaneous breathing activity are still controversial. Because no specific pharmacological therapy revealed beneficial effects until today, adjunctive treatment is actually limited to prone positioning and restrictive fluid balance. Long-term outcome of ARDS survivors is often affected by anxiety and mental health disorders.

[ARDS - An Update - Part 1: Epidemiology, Pathophysiology and Diagnosis]. / ARDS ­ Ein Update ­ Teil 1: Epidemiologie, Pathophysiologie und Diagnostik.

The Acute Respiratory Distress Syndrome (ARDS) is defined by hypoxemic respiratory failure caused by inflammatory response within the lung usually requiring invasive mechanical ventilation. Despite more than 50 years of research numerous issues regarding epidemiology, pathophysiology and diagnosis remain unclear until today: Due to rather unspecific clinical diagnostic criteria incidence of ARDS varies considerably in clinical trials with a range from 4 to 79 cases per 100 000 persons per year. Consequently, mortality is also highly variable from about 40 to 60% in severe ARDS. Pathophysiology is mainly characterized by granulocyte infiltration of the lung thereby inducing interstitial and intra-alveolar lung edema with surfactant depletion and atelectasis formation. However, it is unknown whether pulmonary and extrapulmonary causes and risk factors for ARDS are accompanied by different pathophysiologic processes due to primary endothelial and epithelial injury. Thus, possible benefits of corresponding biomarker panels for the differentiation of endothelial and epithelial lung injury are also speculative until today. Therefore, ARDS diagnosis is still based on clinical findings and radiological imaging.

Preserving spontaneous breathing during mechanical ventilatory support: an old yet fascinating story.

Facilitation of early spontaneous breathing activity is the most important measure to shorten weaning and avoid ventilator-induced lung injury and diaphragmatic injury in mechanically ventilated patients. However, the optimal degree of spontaneous muscle activity and ventilator support remains to be determined. Furthermore, effectiveness in relation to the pathophysiology of respiratory failure is unclear. In this regard the experimental study by Saddy and colleagues reveals interesting insights into the pathophysiology of ventilator-induced injury. More important, their results raise important questions that should be evaluated in further studies.

[Surgical therapy and critical care medicine in severely burned patients - Part 2: the basics in definite care]. / Operative Therapie und Intensivmedizin bei Schwerbrandverletzten - Teil 2: Grundzüge der Weiterversorgung.

Critical care medicine in severely burned patients should be adapted to the different pathophysiological phases. Accordingly, surgical and non-surgical therapy must be coordinated adequately. Initial stabilization of the burn victim during the first 24 hours (Surgical therapy and critical care medicine in severely burned patients - Part 1: the first 24 ours, AINS 9/12) is followed by a long lasting reconstructive period. During this time calculated fluid replacement to compensate evaporative losses by large bourn wounds is as essential as reconstruction of the integrity of the skin and the modulation of metabolic consequences following severe burn injury. Special attention has to be paid to local and systemic infections.

[Surgical therapy and critical care medicine in severely burned patients - Part 1: the first 24 ours]. / Operative Therapie und Intensivmedizin bei Schwerbrandverletzten - Teil 1: die ersten 24 Stunden.

Critical care medicine in severely burned patients should be adapted to the different pathophysiological phases. Accordingly, surgical and non-surgical therapy must be coordinated adequately. Initial wound care comprises topical treatment of less severely injured skin and surgical debridement of severely burned areas. The first 24 hours of intensive care are focused on calculated fluid delivery to provide stable hemodynamics and avoid progression of local edema formation. In the further course wound treatment with split-thickness skin grafts is the major aim of surgical therapy. Critical care is focused on the avoidance of complications like infections and ventilator associated lung injury. Therefore, lung-protective ventilation strategies, weaning and sedation protocols, and early enteral nutrition are important cornerstones of the treatment.

[Emergency Cricothyrotomy - step by step]. / Notfallkoniotomie ­ Schritt für Schritt.

Emergency cricothyrotomy is a live saving intervention to rapidly gain access to the airways in patients who cannot be intubated nor ventilated. Considering complications such as bleeding, thyroid and cricoid cartilage injury and creation of a false tract emergency cricothyrotomy should not be performed until non-invasive attempts including video laryngoscopy and the use of supraglottic airway devices have been exploited within a fixed difficult airway management algorithm. Methods of emergency cricothyrotomy can be differentiated in a catheter-over-needle, Seldinger-wire and surgical technique. However, success is less dependent from the choice of method but from individual experience and training. Despite a lack of evidence due to its infrequent use cricothyrotomy generally results in an acceptable success rate. In this review a selection of commercially available cricothyrotomy sets is presented, indications for their use are outlined and their handling is described.

Using Gated Recurrent Unit Networks for the Prediction of Hemodynamic and Pulmonary Decompensation.

This paper presents a new medical severity scoring system, used to assess the risk of hemodynamic and pulmonary decompensation for patients being treated in intensive care units. The score presented here includes drug circulatory support and ventilation mode data for the evaluation of the patient's biosignals and laboratory values. It is shown that Gated Recurrent Unit-based neural networks are able to predict the maximal severity class within a 24 hour prediction time-frame (hemodynamic: 0.85 AUROC / pulmonary: 0.9 AUROC), and can estimate the underlying decompensation score for prediction times of up to 24 hours with mean errors of 6.3% of the maximal possible pulmonary, and 9.6% of the hemodynamic score. These results are based on 60h observation period. Clinical Relevance- Hemodynamic and pulmonary decom-pensation are life threatening dynamic events that can lead to death of patients. Early detection of these incidents is essential in order to intervene therapeutically and to improve survival chances. In everyday intensive care physicians are confronted with a vast number of laboratory values and vital parameters. There is a risk that early stages of hemodynamic and pulmonary decompensation are misjudged. The implementation of robust warning systems could support physicians in detecting these critical events and initiate therapeutical intervention in time which would achieve significant reduction of patient mortality.

Efficacy and safety of early target-controlled plasma volume replacement with a balanced gelatine solution versus a balanced electrolyte solution in patients with severe sepsis/septic shock: study protocol, design, and rationale of a prospective, randomized, controlled, double-blind, multicentric, international clinical trial : GENIUS-Gelatine use in ICU and sepsis.

BACKGROUND: Sepsis is associated with capillary leakage and vasodilatation and leads to hypotension and tissue hypoperfusion. Early plasma volume replacement is required to achieve haemodynamic stability (HDS) and maintain adequate tissue oxygenation. The right choice of fluids to be used for plasma volume replacement (colloid or crystalloid solutions) is still a matter of debate, and large trials investigating the use of colloid solutions containing gelatine are missing. This study aims to investigate the efficacy and safety of plasma volume replacement using either a combined gelatine-crystalloid regime (1:1 ratio) or a pure crystalloid regime. METHODS: This is a prospective, controlled, randomized, double-blind, international, multicentric phase IV study with two parallel groups that is planned to be conducted at European intensive care units (ICUs) in a population of patients with hypovolaemia in severe sepsis/septic shock. A total of 608 eligible patients will be randomly assigned to receive either a gelatine-crystalloid regime (Gelaspan® 4% and Sterofundin® ISO, B. Braun Melsungen AG, in a 1:1 ratio) or a pure crystalloid regime (Sterofundin® ISO) for plasma volume replacement. The primary outcome is defined as the time needed to achieve HDS. Plasma volume replacement will be target-controlled, i.e. fluids will only be administered to volume-responsive patients. Volume responsiveness will be assessed through passive leg raising or fluid challenges. The safety and efficacy of both regimens will be assessed daily for 28 days or until ICU discharge (whichever occurs first) as the secondary outcomes of this study. Follow-up visits/calls will be scheduled on day 28 and day 90. DISCUSSION: This study aims to generate evidence regarding which regimen-a gelatine-crystalloid regimen or a pure crystalloid regimen-is more effective in achieving HDS in critically ill patients with hypovolaemia. Study participants in both groups will benefit from the increased safety of target-controlled plasma volume replacement, which prevents fluid administration to already haemodynamically stable patients and reduces the risk of harmful fluid overload. TRIAL REGISTRATION: The European clinical trial database EudraCT 2015-000057-20 and the ClinicalTrials.gov Protocol Registration and Results System ClinicalTrials.gov NCT02715466 . Registered on 17 March 2016.

Semi-fluorinated alkanes as carriers for drug targeting in acute respiratory failure.

Partial liquid ventilation (PLV) with perfluorocarbons may cause pulmonary recruitment in acute lung injury (ALI). Semi-fluorinated alkanes (SFAs) provide biochemical properties similar to perfluorocarbons. Additionally, SFAs are characterized by increased lipophilicity. Therefore, SFA-PLV may be considered for deposition of certain therapeutic drugs into atelectatic lung areas. In this experimental study SFA-PLV was evaluated to demonstrate feasibility, pulmonary recruitment, and efficacy of drug deposition. Feasibility of SFA-PLV was determined in pigs with and without experimental ALI. Animals were randomized to PLV with SFAs up to a cumulative amount of 30 mL x kg⁻¹ or to conventional mechanical ventilation. Pulmonary recruitment effects were determined by analyzing ventilation-perfusion distributions. Efficacy of intrapulmonary drug deposition was evaluated in further experiments by measuring drug serum concentrations in the course of PLV with SFA-dissolved α-tocopherol and ibuprofen. Increasing SFA doses caused progressive reduction of intrapulmonary shunt in animals with ALI, indicating pulmonary recruitment. PLV with SFA-dissolved α-tocopherol had no effect on serum levels of α-tocopherol, whereas PLV with SFA-dissolved ibuprofen caused a rapid increase of serum levels of ibuprofen. The authors conclude that SFA-PLV is feasible and causes pulmonary recruitment in ALI. Effectiveness of drug deposition in the lung obviously depends on the partitioning drugs out of the SFA phase into blood.

Effectiveness of nitric oxide during spontaneous breathing in experimental lung injury.

Inhaled nitric oxide (iNO) improves gas exchange in about 60% of patients with acute respiratory distress syndrome (ARDS). Recruitment of atelectatic lung areas may improve responsiveness and preservation of spontaneous breathing (SB) may cause recruitment. Accordingly, preservation of SB may improve effectiveness of iNO. To test this hypothesis, iNO was evaluated in experimental acute lung injury (ALI) during SB. In 24 pigs with ALI, effects of 10 ppm iNO were evaluated during controlled mechanical ventilation (CMV) and SB in random order. Preservation of SB was provided by 4 different modes: Unassisted SB was enabled by biphasic positive airway pressure (BIPAP), moderate inspiratory assist was provided by pressure support (PS) and volume-assured pressure support (VAPS), maximum assist was ensured by assist control (A/C). Statistical analysis did not reveal gas exchange improvements due to SB alone. Significant gas exchange improvements due to iNO were only achieved during unassisted SB with BIPAP (P <.05) but not during CMV or assisted SB. The authors conclude that effectiveness of iNO may be improved by unassisted SB during BIPAP but not by assisted SB. Thus combined iNO and unassisted SB is possibly most effective to improve gas exchange in severe hypoxemic ARDS.

Extracorporeal gas exchange in acute lung injury: step by step towards expanded indications?

Extracorporeal membrane oxygenation (ECMO) is widely accepted as a rescue therapy in patients with acute life-threatening hypoxemia in the course of severe acute respiratory distress syndrome (ARDS). However, possible side effects and complications are considered to limit beneficial outcome effects. Therefore, widening indications with the aim of reducing ventilator induced lung injury (VILI) is still controversial. Consequently, technological progress is an important strategy. Miniaturized ECMO systems are believed to simplify handling and reduce side effects and complications. Mueller and co-workers evaluated such a small-sized device in 60 patients with severe ARDS. They accomplished both the treatment of severe hypoxemia and reduction of VILI, demonstrating feasibility, a moderate rate of severe complications, and a 45% intensive care survival rate. Although neither randomized nor controlled, this study should encourage others to implement such systems in clinical practice. From a strategic perspective, this is another small but useful step towards implementing extracorporeal gas exchange for the prevention of VILI. It is already common sense that the prevention of acute life-threatening hypoxemia usually outweighs the risks of this technique. The next step should be to prove that prevention of life-threatening VILI balances the risks too.

Low tidal volume ventilation in a porcine model of acute lung injury improves cerebral tissue oxygenation.

BACKGROUND: In study, we investigated the effects of different tidal volumes on cerebral tissue oxygenation and cerebral metabolism in a porcine model of acute lung injury (ALI). We hypothesized that mechanical ventilation with low tidal (LT) volumes improves cerebral tissue oxygenation and metabolism after experimentally induced ALI. METHODS: After inducing experimental ALI by surfactant depletion, we studied two conditions in 10 female pigs: 1) LT volume ventilation with 6 mL/kg body weight, and 2) high tidal (HT) volume ventilation with 12 mL/kg body weight. Variables of gas exchange, hemodynamic, continuous cerebral tissue oxygen tension (p(ti)O2), cerebral microdialysis, and systemic cytokines were analyzed. After induction of ALI, data were collected at 2, 4, and 8 h. The primary end point was the change in p(ti)O2. For group comparisons, a t-test was used. A value of <0.05 was considered to indicate statistical significance. RESULTS: At baseline and after induction of ALI, no differences between groups were found in p(ti)O2; however, p(ti)O2 was significantly lower in the HT group after 4 and 8 h. PaO2 and PaCO2 showed no significant differences between the groups at all timepoints. Regarding cerebral microdialysis, a significantly higher level of extracellular lactate could be demonstrated after 2, 4, and 8 h in the HT group. The release of cytokines resulted in higher values for interleukin-6 and interleukin-8 in the HT group. CONCLUSION: Protective ventilation with LT yielded a significant improvement in cerebral tissue oxygenation and metabolism compared to HT ventilation in a porcine model of ALI. There was dissociation between arterial and cerebral tissue oxygenation. Cerebral oxygenation and metabolism might have possibly been impaired by a more distinctive inflammatory response in the HT group.

Direct intra-abdominal pressure monitoring via piezoresistive pressure measurement: a technical note.

BACKGROUND: Piezoresistive pressure measurement technique (PRM) has previously been applied for direct IAP measurement in a porcine model using two different devices. Aim of this clinical study was to assess both devices regarding complications, reliability and agreement with IVP in patients undergoing elective abdominal surgery. METHODS: A prospective cohort study was performed in 20 patients randomly scheduled to receive PRM either by a Coach-probe or an Accurate(++)-probe (both MIPM, Mammendorf, Germany). Probes were placed on the greater omentum and passed through the abdominal wall paralleling routine drainages. PRM was compared with IVP measurement by t-testing and by calculating mean difference as well as limits of agreement (LA). RESULTS: There were no probe related complications. Due to technical limitations, data could be collected in 3/10 patients with Coach and in 7/10 patients with Accurate++. Analysis was carried out only for Accurate++. Mean values did not differ to mean IVP values. Mean difference to IVP was 0.1 +/- 2.8 mmHg (LA: -5.5 to 5.6 mmHg). CONCLUSION: Direct IAP measurement was clinically uneventful. Although results of Accurate++ were comparable to IVP, the device might be too fragile for IAP measurements in the clinical setting. Local ethical committee trial registration: EK2024.

Comparison of two in vivo microscopy techniques to visualize alveolar mechanics.

OBJECTIVE: In conventional in vivo microscopy, a three dimensional illustration of tissue is lacking. Concerning the microscopic analysis of the pulmonary alveolar network, surgical preparation of the thorax and fixation of the lung is required to place the microscope's objective. These effects may have influence on the mechanical behaviour of alveoli. Relatively new methods exist for in vivo microscopy being less invasive and enabling an observation without fixation of the lung. The aim of this study was to compare a fibered confocal laser scanning microscopy (FCLSM) with optical coherence tomography (OCT) in a mouse and a rabbit model. Moreover, FCLSM was also used endoscopically in the rabbit model. METHODS: Smallest possible thoracic windows were excised at the lower margin of the upper right lung lobe and an interpleural catheter inserted before re-coverage with a transparent membrane foil. The OCT-scanner was positioned by a motor driven translation stage. The imaging was gated to endinspiratory plateau. For CLSM, Fluorescein 0.1% was given into the central venous streak line. The confocal probe with a diameter of 650 microm was carefully positioned at the very same lung region. Images were directly recorded real-time and the observed region qualitatively compared with FD-OCT images. Additionally, in the rabbit model, CLSM was used endoscopically under bronchoscopic sight control. In a postprocessing analysis, images taken were analyzed and compared by using an "air index" (AI). RESULTS: In the mouse model, the very same region could be re-identified with both techniques. Concerning alveolar shape and size, qualitatively comparable images could be gained. The AI was 40.5% for the OCT and 40.1% for the CLSM images. In the rabbit, even an endoscopic view on alveoli was possible. Likewise AI was 43.2% for CLSM through the thoracic window and 43.6% from endoscopically. For the OCT an AI of 44.6% was analysed in the rabbit model. CONCLUSIONS: Both FD-OCT and CLSM provide high-resolution images of alveolar structure giving depth information that is beneficial to conventional microscopy. CLSM also facilitates endoscopic view on alveoli being well comparable to images gained through a thoracic window.

[The Laryngeal mask - step by step]. / Die Larynxmaske ­ Schritt für Schritt.

Laryngeal masks are supraglottic airway devices developed in the early 1980s. Today, they are frequently used in clinical routine to provide airway access for mechanical ventilation in patients undergoing surgery with a short duration. Moreover, the they have also become integral part of difficult airway management in patients who cannot be intubated by the use of conventional laryngoscopy.Relevant advances have been made to simplify their positioning and improve tightness with the aim to allow for the use of higher airway pressures during mechanical ventilation thereby reducing the risk of gastric insufflation and pulmonary aspiration. Focusing on this goal, several different prototypes have been developed and introduced in clinical practice until today. However, even these new developed laryngeal masks still do not provide reliable protection against pulmonary aspiration until today. Consequently, their use In critical care medicine is still limited to rescue situations with intubation failure.In this review some of the most popular lanryngeal masks are presented, indications for their use are outlined and their handling is described.

Clinical evaluation of an air-capsule technique for the direct measurement of intra-abdominal pressure after elective abdominal surgery.

BACKGROUND: The gold standard for assessment of intraabdominal pressure (IAP) is via intravesicular pressure measurement (IVP). This accepted technique has some inherent problems, e.g. indirectness. Aim of this clinical study was to assess direct IAP measurement using an air-capsule method (ACM) regarding complications risks and agreement with IVP in patients undergoing abdominal surgery. METHODS: A prospective cohort study was performed in 30 patients undergoing elective colonic, hepatic, pancreatic and esophageal resection. For ACM a Probe 3 (Spiegelberg, Germany) was placed on the greater omentum. It was passed through the abdominal wall paralleling routine drainages. To compare ACM with IVP t-testing was performed and mean difference as well as limits of agreement were calculated. RESULTS: ACM did not lead to complications particularly with regard to organ lesion or surgical site infection. Mean insertion time of ACM was 4.4 days (min-max: 1-5 days). 168 pairwise measurements were made. Mean ACM value was 7.9 +/- 2.7 mmHg while mean IVP was 8.4 +/- 3.0 mmHg (n.s). Mean difference was 0.4 mmHg +/- 2.2 mmHg. Limits of agreement were -4.1 mmHg to 5.1 mmHg. CONCLUSION: Using ACM, direct IAP measurement is feasible and uncomplicated. Associated with relatively low pressure ranges (<17 mmHg), results are comparable to bladder pressure measurement.